Abstract Details

Title Treatment of HIV Associated Neurocognitive Disorder Mice with Curcumin Improves Cognitive Deficits

Topic Infectious Disease

Presentation(s) Infectious Disease Posters (7:00 AM-5:00 PM)

Poster/Presentation
Number 021

Objective To determine if curcumin reverses cognitive dysfunction in HIV associated neurocognitive disorders (HAND) mice and correlates with improvement in brain pathology.

Background HAND affects approximately 50% of HIV-infected individuals regardless of combined antiretroviral therapy (cART). Mild cognitive deficits predominate in cART HAND patients, although this may eventually lead to dementia. Therefore, adjunctive therapies need to be developed. Curcumin is a derivative of turmeric used as a spice in curry and is known to abrogate mononuclear phagocyte (MP) inflammatory activity. Brain MP inflammatory activity is believed to be a significant contributor to the pathogenesis of HAND.

Design/Methods Our HAND mouse model enables measurement of cognitive deficits before and after treatments, which simulates important features of potential human trials. Controls (n=8) are injected intracerebrally (IC) with uninfected human monocyte derived macrophages (MDM) and HAND mice (n=16) with HIV-ADA infected MDM. Later they underwent object recognition testing (ORT). Then half (n=8) of the HAND mice received curcumin subcutaneously (SC) qday 50 mg/kg and the other HAND mice saline. After a week of treatment mice again underwent ORT and were sacrificed for brain pathological analyses.

Results ORT demonstrated significant (p< 0.001) cognitive deficits in HAND mice. Repeat ORT after 1 week of SC injections revealed significant improvement (p< 0.045) in HAND mice given curcumin compared to HAND mice given saline. Brain pathology analyses will be performed using a combination of flow cytometry and brain tissue section techniques.

Conclusions Curcumin treatment of HAND mice improves cognition. We predict this improvement will correlate with improved brain MP inflammatory markers. In addition, curcumin treatment will correct neuronal pathology, which typically has shown dendritic abnormalities and AMPA receptor decreases in untreated HAND mice. Ultimately, treatments such as curcumin, which is widely available, may be applicable to HAND patients and in other cognitive disorders where MP inflammatory action plays a role in pathogenesis.

Authors/Disclosures
William R. Tyor, MD, F�鶹��ýӳ�� (Atlanta VAMC) PRESENTER	The institution of Dr. Tyor has received research support from NIH. The institution of Dr. Tyor has received research support from VHA. The institution of Dr. Tyor has received research support from NIH. The institution of Dr. Tyor has received research support from VHA. The institution of Dr. Tyor has received research support from NIH.
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